Ever
since the yeast genome was sequenced seven years ago, researchers have
debated the best way to identify the “true” genes—those
DNA sequences that code for proteins. Now, researchers have sequenced
three more yeast genomes and say that the current list of genes needs
to be revised.

By comparing the new genome sequences with the original, the researchers
uncovered nearly 50 new genes and 70 stretches of DNA that regulate yeast
genes. They also propose that about 500 DNA sequences previously thought
to be genes should be crossed off the list.

The research, published in Nature, goes far beyond bread and beer:
It could serve as a model for identifying every gene in the human genome.
Furthermore, many yeast genes have counterparts in humans, including some
that play a role in cancer.

“This study shows how valuable it is to sequence the genomes of
closely related species,” says Steven L. Salzberg of the Institute
for Genomic Research (TIGR) in Rockville, Maryland, who wrote an accompanying
News & Views article. “If we line up the genomes and see the
same sequences in each species, it tells us that a gene is important.”

“This is just what we need to do, and in fact are doing, with the
human genome,” he adds.

When the budding yeast, Saccharomyces cerevisiae—used to
make beer and bread—was sequenced in 1996, researchers found nearly
6,000 likely genes (based on the length of the sequence and the presence
of specific signals that indicate where genes begin and end). Subsequent
estimates have ranged from 4,800 to 6,400 genes. According to the Nature
paper, the number should be 5,538 genes.

In the new study, Manolis Kellis, a graduate student in Eric S. Lander’s
laboratory at the Whitehead Institute in Cambridge, Massachusetts, and
his colleagues analyzed the three other yeast species and compared them
to S. cerevisiae.

“For each possible gene sequence, we looked to see if there was
evolutionary pressure to preserve that stretch of DNA,” says Kellis.
“We discarded about 500 sequences that were not conserved. Evolution
had no reason to care about these sequences.”

For Kellis, the study’s most exciting discovery was finding more
than 70 new sequences that regulate gene activity.

“We found two types of regulatory sequences,” he says. “Some
sequences act like little tiny traffic lights, telling the gene when to
turn on and when to turn off. Others act as zip codes, or shipping addresses.
They tell the cell where to send the message, once a gene is made into
RNA.”

The researchers also found that the most variation in yeast genes occurs
on the ends of chromosomes, in regions known as telomeres. Telomeres have
not been completely sequenced in the human genome.

“Telomeres get exchanged a lot more rapidly,” says Salzberg.
“My twenty-five cent bet is that the same thing is going on in humans.
I would like to see telomeres sequenced in humans. This is where things
are most likely to be happening, where gene rearrangements are likely
to occur.”

He adds, “We need to finish the human sequence down to the last
base.”